Tagged: Pink1

When miro just can’t let go

 

Stanford University researchers have recently published an interesting report in which they not only propose a novel biomarker for Parkinson’s, but also provide some compelling data for a novel therapeutic approach.

Their research focuses on a protein called Miro, which is involved in the removal of old or faulty mitochondria. Mitochondria are the power stations of each cells, providing cells with the energy they require to do what they do.

Specifically, the researchers found that Miro refuses to let go of mitochndria in people with Parkinson’s (which could act as a biomarker for the condition). They also found that pharmacologically forcing Miro to let go, resulted in neuroprotective benefits in models of Parkinson’s

In today’s post, we will discuss what Miro is, what the results of the new research suggest, and we will consider what will happen next.

 


 

Source: Amazingaccelerators

Every now and then a research report comes along and you think: “Whoa, that’s amazing!”

It a piece of work that breaks down your cynicism (which you have proudly built up over years of failed experiments) and disciplined scepticism (a critical ingredient for a career in scientific research – mantra: ‘question everything’). And for a moment you are taken in by the remarkable beauty of not just good research, but biology itself.

A couple of weeks ago, one such research report was published.

This is it here:

Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models.
Authors: Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X.
Journal: Cell Metab. 2019 Sep 23. [Epub ahead of print]
PMID: 31564441

It’s a really interesting study for several reasons.

So what did they report?

Continue reading

A re-think of PINK

 

The immune system is our main line of defense against a world full of potentially dangerous disease causing agents. It is a complicated beast that does a fantastic job of keeping us safe and well.

Recently, however, there was an interesting study suggesting that a genetic risk factor for Parkinson’s may be associated with an over-reaction from the immune system in response to infection from a common human food poisoning bug.

Specifically, mice who were missing the gene PINK1 literally had an ‘autoimmune reaction’ to the infection – that is the immune system began attacking healthy cells of the body – while normal mice (with intact PINK1 genes) recovered from the infection and went about their business.

In today’s post, we will explore this new research and discuss why we may need to rethink PINK.

 


Source: Huffington Post

I have had a guts full of all this gut research being published about Parkinson’s.

[NOTE 1.: For the unitiated: A “guts full” – Adjective, Kiwi colloquialism. Meaning ‘Had enough of’, ‘fed up of’, ‘endured to the point of tolerance’]

[NOTE 2.: The author of this blog is a Kiwi]

I really can’t stomach anymore of it.

And my gut feeling suggests that there is only more to come. It would be nice though, to have something else… something different to digest.

So what is today’s post all about?

Gut research of course.

But this gut research has a REALLY interesting twist.

Continue reading

Time to resTOR in New Zealand

 

As the amazing Australian Parkinson’s Mission project prepares to kick off, across the creek in my home land of New Zealand, another very interesting clinical trial programme for Parkinson’s is also getting started. The study is being conductetd by a US biotech firm called resTORbio Inc.

The drug being tested in the study is called RTB101.

It is an orally-administered TORC1 inhibitor, and it represents a new class of drug in the battle against Parkinson’s. 

In today’s post, we will look at what TORC1 is, how the drug works, the preclinical research supporting the trial, and what this new clinical trial will involve.

 


Rapa Nui. Source: Chile.Travel

Today’s post kicks off on an amazing south Pacific island… which is not New Zealand.

In 1965, a rather remarkable story began in one of the most remote inhabited places on Earth – the mysterious island of Rapa Nui (or “Easter Island”).

And when we say ‘remote’, we really do mean remote. Did you know, the nearest inhabited island to Rapa Nui is Pitcairn Island, which is 2,075 kilometres (1,289 mi) away. And Santiago (the capital of Chile) is 2,500 miles away – that’s a four-hour+ flight!!!

Rapa Nui is the very definition of remote. It is as remote as remote gets!

Does Amazon deliver to the town of Hanga Roa? Source: Atlasandboots

Anyways, in 1965 a group of researchers arrived at Rapa Nui with the goal of studying the local inhabitants. They wanted to investigate their heredity, environment, and the common diseases that affected them, before the Chilean government built a new airport which would open the island up to the outside world.

It was during this investigation, that one of the researchers – a University of Montreal microbiologist named Georges Nógrády – noticed something rather odd.

What?

At the time of the study, wild horses on Rapa Nui outnumbered humans (and stone statues).

Wild horses roaming the east coast of Rapa Nui. Source: Farflungtravels

But what was odd about that?

Georges discovered that locals had a very low frequency of tetanus – a bacterial infection of the feet often found in places with horses. He found this low incidence of tetanus particularly strange given that the locals spent most of their time wandering around the island barefoot. So Georges decided to divide the island into 67 regions and he took a soil sample from each for analysis.

In all of the vials collected, Nógrády found tetanus spores in just one vial.

Something in the soil on Rapa Nui was extremely anti-fungal.

In 1969, Georges’ collection of soil samples was given to researchers from the pharmaceutical company Wyeth and they went looking for the source of the anti-fungal activity. After several years of hard work, the scientists found a soil bacteria called Streptomyces hygroscopicus which secreted a compound that was named Rapamycin – after the name of the island – and they published this report in 1975:

Title: Rapamycin (AY-22, 989), a new antibiotic
Authors: Vézina C, Kudelski A, Sehgal SN.
Journal: J Antibiot (Tokyo). 1975 Oct;28(10):721-6.
PMID: 1102508              (This report is OPEN ACCESS if you would like to read it)

It is no understatement to say that this was a major moment in biomedical history. So much so that there is actually a plaque on the island commemorating the discovery of rapamycin:

Source: DiscoveryMag

Why was the discovery of ‘anti-fungal’ rapamycin so important?!?

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Exercise: Taking the STING out of Parkinson’s

 

In December of of 2017, the results of a clinical trial suggested that a particular  kind of exercise may have beneficial effects against certain aspects of Parkinson’s. Specifically, a high-intensity treadmill regime was found to be ‘non-futile’ as an intervention for the motor symptoms in de novo (newly diagnosed) Parkinson’s.

Recently, however, new pre-clinical research has been published which reported that when mice with particular Parkinson’s-associated genetic mutations are exercised to exhaustion, they have high levels of inflammation which can exaggerate the neurodegeneration associated with that model of PD.

So naturally, some readers are now asking “So should I be exercising or not?!?”

In today’s post we will review the results of the two studies mentioned above, and discuss why exercise is still important for people with Parkinson’s.

 


Readers are recommended to click on the image above and listen to the music (Michael Sembello’s “Maniac” from 1983) whilst reading this post.

This song was made famous by one particular scene from the 1983 movie “Flashdance” starring Jennifer Beals, in which the lead character undertook an intense dance routine. Ever since that iconic scene, exercise fanatics have long used the music to help get themselves into the mood for their workouts.

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One of my personal life goals. Source: Jobcrusher

Few experts would disagree that the benefits of exercise are many.

Adults who achieve at least 2.5 hours of physical activity per week have:

  • up to a 35% lower risk of coronary heart disease and stroke
  • up to a 50% lower risk of type 2 diabetes
  • up to a 50% lower risk of colon cancer
  • up to a 20% lower risk of breast cancer
  • a 30% lower risk of early death
  • up to an 83% lower risk of osteoarthritis
  • up to a 68% lower risk of hip fracture
  • a 30% lower risk of falls (among older adults)
  • up to a 30% lower risk of depression
  • up to a 30% lower risk of dementia

(Source: NHS)

But what about people with PD? What do we know about exercise and Parkinson’s?

Continue reading

New LRRK2 results: Game changer?

 

Millions of dollars in research funding for Parkinson’s has been poured into the biology and function of just one hyperactive protein. It is called Leucine-rich repeat kinase 2 (or LRRK2). Genetic mutations in the gene that gives rise to this abnormal version of the protein can leave carriers with a higher risk of developing Parkinson’s. 

All of that research funding has resulted in an incredible leap forward in our understanding of LRRK2, which has further led to clinical trials focused solely on LRRK2. Mutations in the LRRK2 gene occur in only 1-2% of the Parkinson’s population, however, which has led to some complaints that too much research is being focused on only a small fraction of the people affected by PD.

New research published this week could silence those complaints.

In today’s post we will discuss a new report suggesting that independent of any genetic mutations, LRRK2 may actually play a role in idiopathic (or spontaneous) forms of Parkinson’s, which means that the treatments being developed for LRRK2 could be beneficial for a wider section of the PD community.

 


sergey_brin

This is Sergey Brin.

He’s a dude.

You may have hear of him – he was one of the founders of a small company called “Google”.

Having changed the way the world searches the internet, he is now turning his attention to other projects.

One of those other projects is close to our hearts: Parkinson’s.

Why is he interested in Parkinson’s?

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Lipid issues in ER = ZZZ issues in PD

New research provides some interesting insight into particular cellular functions – and possibly sleep issues – associated with Parkinson’s.

Researchers in Belgium have recently published interesting findings that a genetic model of Parkinson’s exhibits sleep issues, which are not caused by neurodegeneration, but rather neuronal dysfunction. And as a result, they were able to treat it… in flies at least.

In today’s post, we will review this new research and consider its implications.


Source: Dlanham

I am a night owl.

One that is extremely reluctant to give up each day to sleep. There is always something else that can be done before going to bed. And I can often be found pottering around at 1 or 2am on a week night.

As a result of this foolish attitude, I am probably one of the many who live in a state of sleep deprivation.

I am a little bit nervous about doing the spoon test:

 

 

 

 

 

But I do understand that sleep is very important for our general level of health and well being. And as a researcher on the topic, I know that sleep complications can be a problem for people with Parkinson’s.

What sleep issues are there for people with Parkinson’s?

Continue reading

DUBstop: Oxford-style

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This week multiple research groups at the University of Oxford and Boston-based FORMA Therapeutics announced a collaboration to identify, validate and develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s.

But what exactly are DUB inhibitors? And how do they work?

In today’s post, we will answer these questions, look at what the new collaboration involves, and look at what else is happening with DUB inhibitors for Parkinson’s.


dubstep_color_and_white_by_dtfproductions-d3admfb

Source: Blog4dubstep

Dubstep is a genre of electronic dance music that originated in South London in the late 1990s. Only recently -in the 2010s – has the culture really become more mainstream. And while I have a hard time appreciating the heavy bass music (man, I am becoming a grumpy old man before my time), it is amazing to watch some of the dancers who robotically embody this form of music:

The guy on the right is named Marquese Scott. Sometimes he simply defies the laws of physics.

The title of today’s post is a play on words, because rather than doing ‘Dubstep’ we are going to be discussing how to ‘DUB-stop’.

Researchers in Oxford have recently signed an agreement with a US company to focus resources and attention on a new approach for tackling neurodegenerative conditions, including Parkinson’s.

What they are proposing is a complicated biological dance.

Their idea: to stop deubiquitinating (DUB) enzymes.

What are deubiquitinating enzymes?

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Monthly Research Review – January 2018

Today’s (experimental) post provides something new – an overview of some of the major bits of Parkinson’s-related research that were made available in January 2018.


In January of 2018, the world was rocked by news that New Zealand had become the 11th country in the world to put a rocket into orbit (no really, I’m serious. Not kidding here – Click here to read more). Firmly cementing their place in the rankings of world superpowers. In addition, they became only the second country to have a prime minister get pregnant during their term in office (in this case just 3 months into her term in office – Click here to read more about this).

A happy New Zealand prime minister Jacinda Ardine

In major research news, NASA and NOAA announced that 2017 was the hottest year on record globally (without an El Niño), and among the top three hottest years overall (Click here for more on this), and scientists in China reported in the journal Cell that they had created the first monkey clones, named Zhong Zhong and Hua Hua (Click here for that news)

Zhong Zhong the cute little clone. Source: BBC

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FASN-ating PINK research

Pink

In 2018, there is one particular clinical trial that I will be watching, because the drug being tested could have a big impact on certain kinds of Parkinson’s.

The clinical trial is focused on people with cancer and they will be treated with a drug called TVB-2640TVB-2640 is an inhibitor of an enzyme called fatty acid synthase (or FAS). 

In today’s post we will discuss why TVB-2640 might be a useful treatment for certain kinds of Parkinson’s.


Mitochondria

Mitochondria and their location in the cell. Source: NCBI

 

Regular readers of this blog are probably getting sick of the picture above.

I use it regularly on this website, because a.) it nicely displays a basic schematic of a mitochondrion (singular), and where mitochondria (plural) reside inside a cell. And b.) a lot of evidence is pointing towards mitochondrial dysfunction in Parkinson’s.

What are mitochondria?

Mitochondria are the power stations of each cell. They help to keep the lights on. Without them, the party is over and the cell dies.

How do they supply the cell with energy?

They convert nutrients from food into Adenosine Triphosphate (or ATP). ATP is the fuel which cells run on. Given their critical role in energy supply, mitochondria are plentiful (some cells have thousands) and highly organised within the cell, being moved around to wherever they are needed.

Source: Mangomannutrition

What does this have to do with Parkinson’s?

Continue reading

2017 – Year in Review: A good vintage

At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective. 

2017 has been an incredible year for Parkinson’s research.

And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.

In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)


The number of research reports and clinical trial studies per year since 1817

As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.

The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).

PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.

That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.

And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.

So what happened in 2017? Continue reading